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Biomedical subjects

A Fowden

Publications and source records attributed to A Fowden.

9 recordsLinked to original sources

Regulation of placental efficiency for nutrient transport by imprinted genes.

Intrauterine growth and development can impact upon the long-term health of an individual. The fetus is dependent upon the placenta for its supply of nutrients and oxygen from the mother. In turn, the functional capacity of the placenta to supply that demand is under the control of the fetal and maternal genomes. Recent evidence suggests that imprinted genes, a class of genes found in placental mammals whose expression depends on their parental origin, have multiple roles in the placenta. The imprinted genes regulate the growth and transport capacity of the placenta, thereby controlling the supply of nutrients. They may also regulate the growth rate of fetal tissues directly, thereby controlling nutrient demand by the fetus. Recent studies using mice with deletions or disruption of imprinted genes with an altered balance between placental and fetal growth and changes in placental efficiency are indicative of feto-placental signalling of fetal nutrient demand. We propose that signalling mechanisms involving growth demand signals and nutrient transporters are likely to occur and are important for fine tuning normal fetal growth.

Animals↗

The influence of maternal size on placental, fetal and postnatal growth in the horse. II. Endocrinology of pregnancy.

Within-breed artificial insemination and between-breed embryo transfer were carried out in small pony (P) and large Thoroughbred (Tb) mares to create 4 types of horse pregnancy in which the fetus experienced spatial and nutritional deprivation (Tb-in-P; n=8), luxury (P-in-Tb; n=7) or normality (Tb-in-Tb; n=7 and P-in-P; n=7) in utero. Measurement of equine chorionic gonadotrophin (eCG), total conjugated oestrogens and progestagen concentrations in serial peripheral serum samples recovered from all the mares throughout gestation showed that the amount of eCG produced during the first half of gestation was dependent upon the breed of the mare rather than the breed of the fetus being carried. In contrast, the mean total amounts of oestrogens produced, as measured by area under the curve, were significantly greater (P=0.003) in the two types of pregnancy in which a Thoroughbred fetus was being carried (Tb-in-Tb and Tb-in-P) than those in which a pony fetus was gestated (P-in-P and P-in-Tb); the evidence suggests that the Tb fetus may have larger gonads than the P fetus and thereby secrete more C-19 precursor steroids for aromatisation to oestrogens by the placenta. In the final weeks of pregnancy mean plasma progestagen concentrations rose much earlier, and to significantly higher levels (P<0.001), in the Tb-in-P than in the P-in-Tb pregnancies, thereby reflecting the increased fetal stress in the former causing premature maturation of the fetal adrenal gland. This, in turn, resulted in increased secretion of pregnenolone by the adrenal cortex for conversion to progestagens by the placenta.

Analysis of Variance↗

Cannulation in situ of equine umbilicus. Identification by gas chromatography-mass spectrometry (GC-MS) of differences in steroid content between arterial and venous supplies to and from the placental surface.

Equine umbilicus was cannulated in utero and a series of cord plasma samples removed for analysis. After steroid extraction and derivatisation, gas chromatographic-mass spectrometric (GC-MS) analysis demonstrated large differences in steroid content between the plasma samples obtained from the umbilical artery and vein, the blood supplies leading to and from the placental surface, respectively. 3Beta-hydroxy-5,7-androstadien-17-one, dehydroepiandrosterone, pregnenolone, 3beta-hydroxy-5alpha-pregnan-20-one, 5-pregnene-3beta,20beta-diol and 5beta-pregnane-3beta,20beta-diol were identified as major constituents in extracts from umbilical arterial plasma samples, mostly as unconjugated steroids. Together with 5alpha-pregnane-3,20-dione, these steroids were identified in extracts from umbilical venous plasma samples but at significantly reduced levels to those determined in arterial plasma samples. Oestradiol-17alpha, dihydroequilin-17alpha and dihydroequilenin-17alpha were identified in extracts (mostly sulphate-conjugated) from both umbilical arterial and venous plasma samples, much larger amounts being detected in the plasma sampled from, rather than to, the placental surface. Equilin, equilenin, oestrone, oestradiol-17beta, dihydroequilin-17beta and dihydroequilenin-17beta were not detected in the present studies. Isomers of 5(10)-oestrene-3,17beta-diol together with 5(10),7-oestradiene-3,17beta-diol and its possible oxidative artifact, 5(10),7,9-oestratriene-3,17beta-diol, were tentatively identified only in sulphate-conjugated extracts from umbilical venous plasma samples. No glucuronic acid-conjugated steroids could be detected. The implications of this work in the elucidation of the biosynthetic pathways leading to both the formation of oestrogens and C18 neutral steroids at the placental surface are discussed.

Androstadienes↗

Effects of incremental cortisol and adrenalectomy on plasma corticosteroid binding capacity in fetal sheep.

The effects of incremental cortisol infusion or fetal adrenalectomy on plasma corticosteroid-binding capacity (CBC) were examined in sheep fetuses during late gestation (term approximately 150 days). Cortisol, infused from day 120 at 1.5 mg/day for the first 3 days, 2.5 mg/day for the next 5 days, and 3.5 mg/day for the final 2 days, stimulated a significant rise in plasma CBC and immunoreactive corticosteroid binding globulin (CBG). There was a significant positive correlation between individual values for total plasma cortisol concentrations and CBC values. In contrast, fetal adrenalectomy at day 115 prevented the rise in plasma CBC found in intact fetuses at term. These experiments show that exogenous cortisol, given in a manner that mimics the prepartum rise in fetal plasma cortisol, stimulates CBG biosynthesis, whereas abolition of the cortisol rise prevents the increase in CBG. The study provides strong support for the proposal that the prepartum increase in CBG biosynthesis in fetal sheep occurs in response to the progressive rise in adrenal cortisol output by the fetus towards term.

Adrenal Cortex Hormones↗

The role of parathyroid hormone-related protein in calcium homeostasis in the fetal pig.

The concentrations of plasma parathyroid hormone-like bioactivity and parathyroid hormone-related protein (1-86) (PTHrP) immunoreactivity were both higher in fetal pigs than in their mothers during the last 3 weeks of gestation. Both activities changed inversely with alterations in the plasma ionized calcium concentration. The data suggest that PTHrP may have a role in calcium homeostasis in the fetal pig, similar to its postulated role in sheep in the stimulation of calcium transport across the placenta.

Animals↗

The effects of pancreatectomy on the plasma concentrations of insulin-like growth factors 1 and 2 in the sheep fetus.

The effects of hypoinsulinaemia and altered metabolite concentrations on the fetal plasma concentrations of insulin-like growth factors (IGF) have been investigated in chronically catheterized fetal sheep made insulin deficient by pancreatic ablation. Fetal pancreatectomy reduced significantly the plasma IGF-1 concentration and increased plasma IGF-2 activity in comparison with the values observed in sham operated fetuses. Mean plasma IGF-1 concentrations in the sham operated and pancreatectomized fetuses were 18.6 +/- 3.1 ng/ml (n = 7) and 13.4 +/- 1.4 ng/ml (n = 13) respectively. When all the data were combined, there was a significant positive correlation between the plasma concentrations of IGF-1 and insulin in utero. The mean IGF-2 activity was 2349 +/- 83 ng/ml (n = 7) in the sham operated fetuses and 3800 +/- 532 ng/ml in the pancreatectomized animals (n = 13). Plasma IGF-2 activity was correlated positively with plasma glucose, fructose and alpha-amino nitrogen levels and inversely related to the plasma insulin concentration in utero. These observations demonstrate that the fetal pancreas is essential for normal IGF production in the fetus and suggest that insulin, substrate availability and the IGFs may interact in the regulation of fetal growth.

Animals↗

Studies on equine prematurity 1: Methodology.

This paper describes the general management of mares and foals during the perinatal period and the methodology used in a collaborative research project on equine prematurity. Sixteen mares with dated pregnancies delivered 45 foals over three breeding seasons (1981 to 1983). In the majority, parturition was induced with oxytocin and/or fluprostenol; the remainder were allowed to foal spontaneously. Pre-colostral milk analysis provided a means of assessing the pre-foaling status of the mare. All were observed and monitored before, during and after parturition and the sampling protocol for both mare and newborn foal is discussed in detail. The foals were assessed for their degree of maturity at birth using behavioural, haematological, acid-base status and other criteria; they were then assigned to groups for further study and tests.

Animals↗

Studies on equine prematurity 6: Guidelines for assessment of foal maturity.

This paper describes criteria used to assess maturity of the newborn foal and their clinical application to field cases of prematurity and dysmaturity. Premature and mature foals may be clearly distinguished by their behavioural and physical characteristics. Measurement of haematological parameters (mean cell volume, total white cell and differential counts), pancreatic beta cell activity (plasma glucose and insulin levels), adrenocortical-medullary function (plasma cortisol, adrenocorticotrophic hormone and catecholamines) and the renin-angiotensin system (plasma renin substrate concentrations) were found useful in evaluating the status of the newborn foal. Confirmation of the initial diagnosis can be made by response to various challenge tests eg, glucose tolerance test, short acting synthetic adrenocorticotrophic hormone (ACTH1-24) and frusemide. In the present investigation a small number of individuals appeared to be intermediate in maturity to the other two groups, indicating that a third state of maturity may be identified. The clinical implications of this work suggest that cortisol replacement therapy and administration of long acting synthetic ACTH1-24 may be of benefit.

Adrenocorticotropic Hormone↗